Our studies have dealt with three areas. First, we have evaluated the effect of liver disease in man (cirrhosis and viral hepatitis) on the disposition of various sedatives and analgesics (diazepam, meperidine and phenobarbital). Our data indicate that the elimination of all three drugs is impaired significantly in the setting of cirrhosis, although the effect is only modest for phenobarbital. Decreased removal of diazepam and meperidine is also seen in patients with acute viral hepatitis, whereas phenobarbital half life is not altered significantly. These changes in the half life of these drugs in cirrhosis is primarily due to their decreased clearance by the diseased liver. Second, our studies have shown that severe thiamine deficiency induced by dietary means in experimental animals causes a rapidly reversible impairment of C14-thymidine incorporation into brain DNA. Pending analysis of the thymidine pool (and its phosphorylated derivatives) in the brain, we interpret our data as showing decreased DNA synthesis in thiamine-depleted brain. Third, we have investigated the effect of folate deficiency on intestinal thiamine absorption. Our studies show that folate deficiency causes a decrease in intestinal absorption of low (0.5 micron M) but not high (17.5 micron M) concentrations of thiamine hydrochloride. The low folate induced impairment of thiamine absorption was reversed with folate restitution. These findings are interpreted as consistent with dual mechanisms of thiamine absorption, saturable and active at low and passive at high concentrations of the vitamin. Folate apparently is involved in the active absorptive process of thiamine.